Diagnosis and complications of renovascular hypertension in children: literature data and clinical observations.

INTRODUCTION
Renovascular hypertension in children is a very rare illness. It occurs as a result of the imbalance between hypotensive and hypertensive systems. Renal ischaemia (95% of the cases) and the shortening of hipotensive factors (5% of the cases) are responsible for the production mechanism of renovascular hypertension in children. In order to make an early diagnosis regarding the renovascular hypertension in all children suffering from renovascular illnesses, blood pressure must be taken correctly and repeatedly.


MATERIALS AND METHODS
This paper is a case study on 19 children with renovascular hypertension, aged between 2 and 15 years old. Most cases were divided into two groups: subjects aged 4-7 years old and subjects aged 8-12 years old. Each group represents 34.2% of all cases. The diagnosis of renovascular hypertension in those 19 children was established after correctly taking the blood pressure and comparing it with the normal values for each age. Hypertension was diagnosed before knowing its cause in 8 neglected cases. The blood pressure was repeatedly taken in the other 11 children suffering from renovascular illnesses and the diagnosis of hypertension was early established when blood pressure values increased. Previously, blood pressure was normal in these 11 cases.


RESULTS
The etiopathogenical diagnosis showed parenchymal diseases in 12 cases--63.1%. Seven patients suffered from renovascular lesions--36.9%. Laboratory exams, radiology, imagistic exams, arteriography and scintigraphy were steps taken in order to establish the etiopathogenical diagnosis. These exams showed the next direct causes of renovascular hypertension: bilateral chronic pyelonephritis in 4 cases--21.4%, hydronephrosis in 3 cases--16.2%, congenital renal hypoplasia in 2 cases--10.4% and doubled kidney in 2 cases--10.4%. The other 8 cases presented acute glomerulonephritis, unilateral renal agenesis, horseshoe kidney, unilateral pyelonephritis, renal artery agenesis, renal trauma, renal abcess and Wilms tumor, one case of each illness--5.2%. The major complications were: retinopathy, chronic renal failure and stroke.


CONCLUSIONS
Laboratory data are just a hint in diagnosing renovascular hypertension. However, radiology, imagistic exams, arteriography and scintigraphy are compulsory in the renourinary status and etiopathogenical diagnosis.


Introduction
The diagnosis of renovascular hypertension is established by correctly taking the blood pressure and comparing the results with normal values for each age.
Normal values of blood pressure in children according to age are showed below:

Age
Normal values (mmHg) In order to avoid stressing the child and obtain values close to normal, blood pressure is taken after lying in bed for 15 minutes.
Blood pressure is taken three times at 10 minutes intervals after the 15 minutes repose. The value close to one of the other two values is considered the real blood pressure value.
Hypertension in adults is often idiopatic. However, hypertension in children and adolescents is a hint for a renal illness like acute glomerulonephritis, chronic glomerulonephritis, pyelonephritis, renal malformation or, rarely, coarctation of the aorta, pheocromocitoma, primary hyperaldosteronism, Cushing syndrome.
The cause of hypertension is established after gathering data from: Anamnesis: the presence of a renal illness or malformation.
Clinical exam: signs of renal injury and hypertension.

Materials and methods
Among the patients of our study (

Investigations
Laboratory data The illnesses producing renovascular hypertension may also induce the urinary syndrome. In our study the following laboratory data were observed: Congenital renoureteral malformations induced many cases of urinary infection -9 patients (47,4%). Five cases of urinary infection also presented renal lesions and only 3 patients had leucocytury -15,8%. The proteinury -21,1% -was moderate under 1-2 grams ‰. Studying 300 cases of idiopatic hypertension and 34 of renovascular hypertension, Bedos et al. [1] conclude that the presence of proteinury is worthless. In 2 cases -10,5% -the laboratory data were missing and paraclinical exams showed right renal agenesis or horseshoe kidney, explaining the hypertension. The hematury was observed in one case -5,2% -with dark urine and focal glomerulonephritis. The poor symtomatology made the diagnosis in horseshoe kidney case difficult. Dajani [2,3] observes three types of horseshoe kidney: a) patients without clinical and laboratory signs; b) cases with nausea and abdominal pain; c) horseshoe kidney with secondary lesions (complications like infections, lithiasis, hypertension).

Radiological and imagistical exams
The evolution of radiological exams made the complex investigation of the entire reno-urinary tract possible.
The radiological investigation became the most important step in diagnosing urinary illnesses in children. The radiological exams used in diagnosing renovascular hypertension are: ecography, urography, cystoscopy, retrograde pyelography, mictional cystography and renal arteriography. a) The duplex color Doppler ultrasonography is the less invasive and the less expensive screening method [4] . The advantages of this method include gathering data about renal artery and its intrarenal branches blood flow and the possibility of calculating the resistivity index (R.I.). This index correlates to the fibrous and atrophic lesions induced by renal artery stenosis, the main cause of renovascular hypertension in children. [5] The ultrasonography is an efficient method in determining the renal size. The susceptibility of renal artery stenosis is suggested by any difference between the kidneys over one centimeter in the absence of a known renal pathology. [4] The disadvantages of the method are: the prolonged examining time -over an hour, the dependence of the results on examiner's skills and on patient's characteristics (young child unable to cooperate with the examiner, gaseous distension of the bowels, obesity). [6] The sensitivity and specificity of the method as its predictive value are different from one case to another. This screening method of the renal artery stenosis is available mostly in specialized centers. [7] b) The urography shows parenchymal and pyelocaliceal alterations consecutive to renal vascular anomalies or congenital malformations. We noticed the following urographic aspects among our cases: Most frequent -31,8%, the urography showed secretion and concentration alterations determined by urinary infection that involved renal parenchyma ( fig. 1 and 2). In 4 cases -21,1%, the urography suggested an aberrant renal vessel due to the vascular print on lumbar ureter. The doubled kidney found in 10,5% of the cases was revealed by a bilateral doubled renal shadow on urography. All the other urographic aspects in the table counted for 5,2% of all cases. Studying 334 patients with hypertension, Bedos et al. [8] found other signs besides intravenous urography in 82% of the cases: abdominal murmur, albuminuria or isotopic renogram alteration.

c)
The cystoscopy is performed when we suspect a vesicoureteral reflux. This exam, performed either on full or empty bladder, provides important data about the size of the ureteral orifice, the development of trigonal muscle fibers, the number of vesical wall trabecles and the laterally movement of ureteral orifices when bladder is filling. [9] Besides inflammatory lesions, vesical trabeculisation or a diverticle close to meatus, the cystoscopy can evaluate: ureteral meatus position; ureteral meatus morphology; submucous ureteral route lenght. d) When renal function is poor, the retrograde pyelography is performed in order to observe the whole excretive tract. The retrograde pyelography was used in 2 cases of all 19 children -10,5%.
Observation 1 The patient C.G., aged 14, had secretion and concentration alterations that led to the impossibility of excretive tract visualisation. Retrograde pyelography was performed and we observed hydronephrosis due to an aberrant renal vessel on a right hypoplasic kidney (Fig. 3). The retrograde pyelography occured during the second admission when concentration and secretion alterations were evolved. The urography and descendent cystography suggested 12 cases of vesicoureteral reflux. For confirmation, mictional cystography was performed using contrast into bladder and producing three pictures: after filling the bladder, mictional and postmictional. The mictional cystography is a benign radiological exam. If performed correctly, using the probes only once, it would not determine uretral trauma, or infections. The exam slightly irradiates the gonads so it is better not to use it very often. In our study, the vesicoureteral reflux was confirmed in 6 cases. Three were normal cases, 2 patients had inflammatory collum and one child had vesical residuum. We noted below the described aspects: e) The arteriography is the method of choice [10] in diagnosing hypertension due to renal artery stenosis. This exam was performed when the urography revealed a print on the lumbar ureter -4 cases and in other 3 cases when isotopic renogram showed renal function alterations. The arteriography did not show any sign of renal artery stenosis but only 5 cases of aberrant polar vessels. Studying data from three authors (676 cases), Pison [11] found renal anomalies in 26,6% of the cases. The arteriography is always to be done in hypertension due to renal illnesseses [1] (Bedos şi colab. 1975) because clinical data cannot orientate the diagnosis. This exam is not performed in order to confirm the diagnosis (fig. 4). However, the arteriography is not used in all cases of renovascular hypertension because it can be followed by complications (renal artery thrombosis, posttrauma aneurism, fever, lumbar pain, rash).

Isotopic nefroscintigram and angiotensin-converting enzyme inhibitor test
Renal scintigraphy was used until the sixties. Modern tests consist in doing a series of scintigraphies: one simple scintigraphy at the begining and another scintigraphy 60 minutes after the administration of an angiotensin-converting enzyme inhibitorcaptopril. The marker used in glomerular ultrafiltration is 99Tc-m-DTPA (dietil triamino-penta-acetic acid). [12] If renal artery stenosis is unilateral, the angiotensinconverting enzyme inhibitor administration will diminish the glomerular ultrafiltration of homolateral kidney and increase ultrafiltration of the contralateral kidney. The angiotensinconverting enzyme inhibitor test just  intensifies the existent modifications on the standard nefroscintigram. [4] The disadvantages of this exam are: low sensitivity in renal failure, the difficulty of interpreting the results in renal artery bilateral stenosis, the fake positive results in renal failure of any etiology. [13] The sensitivity of the method varies between 75% and 85%. [14] Among our patients, the scintigraphy was performed in one case after the urography revealed a silent kidney. The scintigraphy showed a non-functional kidney and indicated the nephrectomy.

Observation 2 A child aged 5, male, is admitted with a urinary infection on a renal malformation (left hypoplasic kidney)
. The urography showed the renal shadows asymmetry. The renal scintigraphy revealed lack of isotopic captation in the base of the right kidney. Preoperative, the uroculture was negative. Left nephrectomy is performed. Histopathological exam diagnosed scleroatrophic chronic pyelonephritis.

A. Diagnosis of hypertension in bilateral renal illnesses
Most of the renal parenchymal illnesses can lead to hypertension. Some of them, like glomerulonephritis, renal amyloidosis, and collagenoses are bilateral, other, like chronic pyelonephritis (most of the cases) and congenital parenchymal nephropathies are unilateral. Our study includes 12 cases -63,1% of parechymal illnesses. In order to apply the proper treatment the diagnosis was established first, weather the nephropathy was unilateral or bilateral. This way, the cases which needed to be treated surgically by nephrectomy were selected.
In order to diagnose chronic pyelonephritis it is necessary to reveal the renal infection and its result on kidney. Next tests are performed to show the renal infection: 1.cytobacteriologic exam-definitive leucocytury over 2000/minute or over 10/mm3 urine; bacteriuria over 100.000 germs/ml urine.
2.Addis-Hamburger test, fractioned, provides the spot of the infection. The frequency of hypertension in pyelonephritis varies from an author to another. Friedman [15] concludes that histological aspects of chronic pyelonephritis were found in 13,5% to 51,5% of patients with renovascular hypertension. After studying 1325 renal biopsies, Casado [16] found chronic pyelonephritis in 150 cases -11,3%. The diagnosis of glomerulonephritic hypertension is set while being based on distinctive elements for this illness: hydropigen syndrome, urinary syndrome, cardiovascular syndrome and renal failure manifestations. In our study we had one case of focal glomerulonephritis -5,2%. Diagnosis is made on hematury, eritrocytes cylinders and moderate proteinury (0,5-1 g‰). These laboratory data frequently appear during a renal infection. The patient has no edema and the hypertension appears episodically in this illness. During the relapses, urinary alterations become permanent and lead to hypertension. There are many types of histopatologic lesions: focused and segmented, endo-mixed proliferative, intra-and exocapillary. Studying 72 adults with renovascular hypertension Ursea [17] identifies 33 patients with glomerulonephritic hypertension: 24 chronic glomerulonephritis, 5 focal glomerulonephritis, 2 proliferative glomerulonephritis and 2 membranous glomerulonephritis. The glomerulonephritis and pyelonephritis are both medical illnesses. The frequency of these illnesses in paediatric surgery is determined by the association with renal malformations in the same children: vesico-ureteral reflux due to an improper implantation of ureters into urinary bladder, aberrant renal vessels or renopyeloureteral duplication.

B. Diagnosis of hypertension in unilateral renal illnesses
1) Renal malformations do not lead to hypertension in all cases. The ectopies, horseshoe kidney and doubled kidney lead to the development of hypertension in most of the cases. a) Congenital renal hypoplasia was diagnosed in 2 cases -10,5%. In the first case it was associated with a bilateral congenital megaureter and in the second case with renal artery agenesis.
Observation 5 After multiple admissions, the patient, aged 14, is transffered from an ophtalmological clinic to establish the diagnosis. The patient is admitted with retinopathy and hypertension -240/160mmHg. Clinical exam showed discreet renal edema. The laboratory exams excluded pyelonephritis and pheocromocitoma: urine cytobacteriologic exam was negative and vanilmandelic acid dosage in urine was normal (2,52mg‰). Renal functional exams were also normal. We thought of a renal malformation and performed a urography that showed a unique right kidney and suggested a left polar vessel, based on a tonus alteration of the left ureter, without dilatation.
The aortography and renal arteriography show a very small, ratatinated kidney on the right side during the nephrographic phase ( fig. 5). On the left, two large renal arteries vascularise a big kidney. The cystoscopy reveals increased and prolonged ureteral orifices. The cystography leads to bilateral vesicoureteral reflux as diagnosis.
Surgery is performed for hypoplasic kidney and bilateral vesico-ureteral reflux (fig. 6). The volume of the right kidney is significantly diminished but its architecture is normal. We practiced right nephrectomy. The histopatological exam on the removed kidney indicated an aglomerular segmental hypoplasia. The hypertension became moderate from severe after surgery. The cytobacteriological exam revealed a renal infection after 30 days. The vesico-ureteral reflux and especially the urinary infection with reflux on unique kidney imposed the ureter reimplantation through Leadbetter -Politano method. Subsequently, the blood pressure became normal.

b)
The doubled kidney is different from the supernumerary kidney. This malformation consists of a big, unilateral or bilateral kidney with two basinets and distinctive vascularisation for the two segments of its construction. This kidney has a symphysis at the adjacent poles. Sometimes the borderline between the two segments is difficult to trace. The diagnosis is establised on urography that shows the volume of the kidney and its doubled basinet and ureter with ureterohydronephrosis. Our study noted two cases -10,5% of bilateral doubled kidney with pyeloureteral bifidity. Niculescu [18] did not find hypertension in any of the three cases of doubled kidney studied. Tcherdokoff si Milliez [10,19,20,21] found this anomaly in one of 21 hypertensive patients and in one of 152 normotensive patients. c) Renal agenesis represents the lack of any renal tissue. The excretive function is performed by the controlateral kidney if it is normal. In such cases, renal agenesis is discovered at routine investigations for local and general illness or at necropsy. In our case, the renal agenesis was associated with an ectopic cystic dilatation of the right ureter. The patient was admitted for enuresis. The urography revealed a normal left kidney and lack of opacity of the right kidney. Multiple radiotransparent images were contoured over the bladder. The renal scintigraphy showed the absence of the right kidney. The hypertension and the right ectopic ureter suggested a hypoplasic kidney although the scintigraphy showed the lack of any renal tissue on the right side. Literature data did not signalize any case of an ectopic cystic dilatated ureter on the same side with the missing kidney. The discussions over the case revealed the fact that some physicians consider it impossible for hypertension to appear in a case with an absent kidney, the contralateral kidney is healthy and a ureter malformation is present. The exploratory laparatomy elucidated the case and demonstrated in the same time that the presence of a ureteral malformation can trigger the hypertensive system even on a healthy functional kidney. This anomaly is found between 1,3 and 1,6‰ at necropsy.

d)
The horseshoe kidney rarely determines hypertension. The diagnosis is easily established because the urography is characteristic.
Nicanor Coban [22,23] described one case of horseshoe kidney accompanied by hypertension. Dajani noticed a sign that can be patognomonical in an astenic child with minimal elevated blood pressure: the hyperextension of the rahis produces a pain that ceases when the column comes to normal.

2)
Unilateral chronic pyelonephritis was present in the case of a single patient -5,2%. The diagnosis was paraclinical: Congenital hypoplasic kidney. Histopatological exam showed a sclero-atrophic pyelonephritis after nephrectomy. In this case, the hypoplasic aspect of the left kidney on urography was determined by the renal parenchyma atrophy. Vexler [24] considered renal hypoplasia to be a parenchymal atrophy.

C. Diagnosis of hypertension in renovascular illnesses
In order to diagnose direct vascular lesions some steps must be followed: clinical examination, case selection for arteriography, arteriography and the determination of stenosis functional significance. 33,6% of 104 arteriographies are found abnormal by Chamberlin [25], but only 4 -3,8% of these benefit from surgical treatment. Indirect vascular lesions were present in 6 of the 19 cases, but only 3 of the 6 cases had hydronephrosis.
The laboratory exams have the privilege to diagnose hydronephrosis: plain radiography and urography. These investigations establish the diagnosis of hydronephrosis. The type of hydronephrosis, primary or secondary, is revealed by ecography, scintigraphy and arteriography. The obstructive urologic illnesses with acute manifestations may induce hypertension to one patient of ten. Studying 252 patients with obstructive uropathy, Schwartz [26,27] found